Allopurinol Prescription Research Articles

Allopurinol use and risk of multiple sclerosis.

Low uric acid levels have been observed in patients with multiple sclerosis (MS). As allopurinol is commonly used to lower uric acid in gout patients, this study examined allopurinol use in individuals with MS during the five years before diagnosis, compared to a matched control group. This nationwide case-control study used Danish health registry data. 9,063 individuals diagnosed with MS between 2008 and 2023 were included on the day of MS diagnosis, while 90,630 controls, were matched from the general population. Controls were matched on age, gender, place of residence, and inclusion date. Allopurinol prescriptions were tracked annually for five years prior to the inclusion date. The primary outcome was the odds ratio of allopurinol use in MS patients compared to controls, analyzed using conditional logistic regression. In the five years prior to the MS diagnosis or matching date for controls, allopurinol use was consistently lower in MS cases. In total, 0.30% (n = 27) of MS cases had at least one allopurinol prescription, compared to 0.62% (n = 558) of controls, corresponding to an odds ratio of 0.48 (95% CI: 0.33-0.71). Individuals diagnosed with MS had significantly lower allopurinol use in the five years preceding their diagnosis, suggesting an inverse relationship between uric acid levels and MS risk. Reduced uric acid levels may be associated with early MS development, possibly due to its antioxidant properties or metabolic changes. Alternatively, these findings suggest a possible protective effect of allopurinol against MS, warranting further investigation.

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Development of Non-Genetic Risk Stratification Model of Severe Allopurinol Hypersensitivity (NoG-ALLOH Score): A Multicenter Study in Thailand

Background The side effect of allopurinol was severe allopurinol hypersensitivity (SAH). There are two major causes including genetic risk factor, HLA-B*58:01 and non-genetic risk factors including female, old age, renal impairment, inadequate starting dosage of allopurinol and received diuretic. Although HLA-B*58:01 testing is recommended in Thai, the several problems including cost, limitation of the testing and the delay of the result. Therefore, we aimed to use these non-genetic risk factors for developing the model to predict SAH. Method The study was a retrospective observational incidence density sampling. SAH cases were collected from tertiary care medical center which some cases were referred from primary care medical center; where most non-SAH cases were collected from primary care hospitals and tertiary care medical centers. The data of non-genetic factors particularly sex, age, renal function, co-diuresis, starting dosage of allopurinol and serum uric acid (SUA) of non-SAH cases selected the first description of allopurinol. The binary prevalence-weighted logistic regression statistical method was used to develop the prediction models. Three models were developed following general practice. Result Totally, there were 209 cases of SAH and 23,068 cases of non-SAH. Factors that were associated with the development of SAH within 90 days were female, old age (¿ 65 years old), renal impairment, inadequate starting dosage of allopurinol, co-medication(s) with diuretic and high SUA before prescription of allopurinol. Model 1a and model 1b were applied for patients who did not have and have SUA when starting allopurinol, respectively. Model 2 was applied for patients who had all non-genetic risk factors and started allopurinol within 60 days but have not SAH. The area under the receiver operating characteristic curve for model 1a, model 1b and model 2 were 0.72, 0.81 and 0.82, respectively (Figure 1). The performance for each predictions SAH were good. Conclusion Model 1a and model 1b predict SAH for the patients who had their first prescribed allopurinol, model 2 predicts SAH for the patients who had been taken allopurinol within 60 days but no SAH. The scoring system of each model helps clinician to prescribe allopurinol in real clinical practice before the patients develop SAH. The score of 0-1%, 1-2% and 2-100% indicates the low, moderate and high risk, respectively. The low-risk group can start allopurinol. The moderate-risk group considers to start allopurinol with closed monitoring of SAH. The high-risk group suggests to change to other urate lowering agents for preventing SAH (Table 1).

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

Allopurinol Prescription Patterns among Patients Attending Primary Health Care Centers in Qatar: A Retrospective Cross-Sectional Study

Allopurinol Prescription Patterns among Patients Attending Primary Health Care Centers in Qatar: A Retrospective Cross-Sectional Study

Cardiovascular safety of non-steroidal anti-inflammatory drug use for gout: A Danish nationwide case-crossover study

Abstract Background Gout is associated with increased cardiovascular risk through inflammation and shared risk factors. Gout attacks are treated with a uric-lowering drug, such as allopurinol, and an anti-inflammatory drug, such as a non-steroidal anti-inflammatory drug (NSAID). Thus, NSAIDs could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic actions. Yet, no study has examined the cardiovascular safety of NSAIDs for the treatment of gout. Purpose To examine the risk of major adverse cardiovascular events (MACEs) associated with NSAID use in gout patients. Methods We conducted a nationwide, population-based case-crossover study of all Danes ≥18 years of age with first-time gout during 1997–2020, who experienced a MACE (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, or all-cause death) (n=103,522). The patients were identified either via a hospital diagnosis for gout (12%) or via a filling of an allopurinol prescription (88%). The exposures were use of NSAIDs overall and according to subtype (ibuprofen, naproxen, or diclofenac). An individual was considered exposed from the time of a filled prescription until the end of a use period, estimated from average use of two tablets per day. In the case-crossover design, we used four reference dates at 120, 180, 240, and 300 days before the outcome. An individual was considered exposed if the use period covered a reference date or the outcome date. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and MACE. Results NSAID use was overall associated with a 15% decreased risk of MACE (OR=0.85, 95% CI: 0.83–0.87). The ORs of the association between NSAID use and the individual cardiovascular events were 0.91 (95% CI: 0.84–0.99) for myocardial infarction, 0.88 (95% CI: 0.81–0.95) for ischemic stroke, 0.89 (95% CI: 0.83–0.94) for congestive heart failure, 0.80 (95% CI: 0.75–0.85) for atrial fibrillation or flutter, and 0.77 (95% CI: 0.75–0.80) for all-cause death. The decreased risk of MACE was observed for use of ibuprofen (OR=0.91, 95% CI: 0.88–0.95) and naproxen (OR=0.78, CI: 0.70–0.86), but not for use of diclofenac (OR=1.03, 95% CI: 0.97–1.09). Conclusions In patients with first-time gout, use of ibuprofen and naproxen was associated with a slightly decreased cardiovascular risk, whereas diclofenac was not.

Drug-induced Stevens Johnson syndrome and toxic epidermal necrolysis: Interpreting the systematic reviews on immunomodulatory therapies.

Drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are non-immunoglobulin E-mediated severe cutaneous adverse reactions with a high risk of morbidity, mortality, and physical and mental health impact. These are associated with certain high-risk drugs, human leukocyte antigen (HLA)-specific genotypes and ethnicities. HLA class I-restricted oligoclonal CD8 cytotoxic T-cell responses occur at the tissue level in SJS/TEN. Cytotoxic T cells are the T effector cells that result in keratinocyte apoptosis (cell death) mediated by T effector molecules granzyme B, perforin, granulysin, gamma interferon, tumor necrosis factor-alpha, and lipocalin-2. The clinical hallmarks of SJS/TEN include fever, ≥2 mucosal involvements (ocular, oral, and genital), and positive Nikolsky sign with epidermal detachment. Systematic reviews on immunomodulatory treatments remain limited by the paucity of randomized controlled trials, heterogeneity of studies, and non-standardization of outcome measures. Preventive HLA genotype screening before the prescription of carbamazepine and allopurinol may further reduce the incidence of SJS/TEN. The role of immunomodulatory treatments in SJS/TEN is at present not supported by robust evidence from systematic reviews given the lack of randomized controlled trials. The evidence for improved survival with off-label use of corticosteroids plus intravenous immunoglobulins, ciclosporin plus intravenous immunoglobulins, and ciclosporin alone has not been demonstrated by network meta-analyses and meta-regression. In the real-world clinical setting, systemic corticosteroids (in SJS and overlap SJS/TEN), ciclosporin, and etanercept (in TEN) appear to be the off-label treatments currently most widely used.

Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis Patients.

Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol; or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with versus without gout. Outcomes included erythropoietin resistance index (ERI=erythropoiesis stimulating agent dose per week/(hemoglobin×weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). The gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2%-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9%-12%). Both HD and PD patients with gout (versus no gout) were older, were more likely male, had higher body mass index, and had higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate-lowering therapy. After propensity score matching, mean ERI was 3%-6% higher for gout versus non-gout patients while there was minimal evidence of association with clinical outcomes or PROs. In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely under-reported. Gout was not associated with adverse clinical or PROs.

Initiation Dose of Allopurinol and the Risk of Severe Cutaneous Reactions in Older Adults With CKD: A Population-Based Cohort Study

Allopurinol should be started at lower doses in patients with chronic kidney disease (CKD) to avoid adverse effects. We examined the risk of severe cutaneous reactions in older adults with CKD who were newly prescribed allopurinol at varied doses. Population-based cohort study using linked health care databases. Patients in Ontario, Canada (2008-2019) aged≥66 years, with an estimated glomerular filtration rate (eGFR) of<60 mL/min/1.73 m2, and who were new users of allopurinol. A new prescription for allopurinol >100 mg/d versus a dose≤100 mg/d. The primary outcome was a hospital visit with a severe cutaneous reaction within 180 days of starting allopurinol. Secondary outcomes included all-cause hospitalization and all-cause mortality. The exposure and referent groups were balanced on indicators of baseline health using inverse probability of treatment weighting on the propensity score. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. Of 47,315 patients (median age, 76 years; median eGFR, 45 mL/min/1.73 m2), 55% started allopurinol at >100 mg/d. Starting allopurinol at >100 versus≤100 mg/d was associated with an increased risk of a severe cutaneous reaction: number of events (weighted), 103 of 25,802 (0.40%) versus 46 of 25,816 (0.18%), respectively (weighted RR, 2.25 [95% CI, 1.50-3.37]; weighted RD, 0.22% [95% CI, 0.12%-0.32%]. Starting allopurinol at >100 versus≤100 mg/d was associated with an increased risk of all-cause hospitalization but not with all-cause mortality. This study was underpowered to detect risk differences in the association of allopurinol dose with outcomes across eGFR categories (ie, 45-59, 30-44, and<30 mL/min/1.73 m2). Older patients with CKD who started allopurinol at >100 mg/d versus≤100 mg/d were twice as likely to visit a hospital with a severe cutaneous reaction in the next 180 days.

P145 Safety of colchicine or NSAID prophylaxis when initiating allopurinol for gout: propensity score-matched cohort studies

Abstract Background/Aims Initiating urate-lowering therapy for gout commonly triggers a gout flare and hence co-prescription of colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis is recommended. However, little is known about the incidence of adverse events associated with prophylaxis. We aimed to determine the risk of adverse events severe enough to warrant seeking healthcare associated with colchicine or NSAID prophylaxis when initiating allopurinol for gout. Methods We conducted two matched retrospective cohort studies, using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) datasets. Adults aged ≥18 years with a Read code for gout and a new allopurinol prescription between 1997 and 2016 were identified. We compared those prescribed (1) colchicine or (2) NSAID prophylaxis with those prescribed no prophylaxis, individually matched by age, sex and propensity to receive prophylaxis, to reduce the impact of confounding by indication. Adverse events were identified in CPRD and HES using Read and ICD10 codes respectively. Associations between colchicine or NSAID prophylaxis and the first occurrence of each outcome were investigated using weighted Cox proportional hazards models. CPRD Gold and Aurum datasets were analysed separately and then combined using 2-stage individual patient data meta-analysis. Results 13,945 individuals who initiated allopurinol with colchicine prophylaxis were matched to 13,945 who initiated without prophylaxis (mean age 63.62 years [95%CI 63.54, 63.70]; 78% male). Diarrhoea was the most common adverse event in the colchicine group, followed by nausea/vomiting, myocardial infarction (MI), neuropathy, myalgia, and bone marrow suppression (Table). Diarrhoea, MI, neuropathy, myalgia, and bone marrow suppression were significantly more common with colchicine prophylaxis compared with no prophylaxis. 22,880 individuals who initiated allopurinol with NSAID prophylaxis were matched to 22,880 who initiated without prophylaxis (mean age 63.34 years [95%CI 63.26, 63.42]; 78% male). Angina, acute kidney injury, MI, and peptic ulcer disease were significantly more common with NSAID prophylaxis than without (Table). Conclusion Gastrointestinal, cardiorenal, myoneuropathic, and haematological adverse events were associated with prophylaxis, although absolute event rates were low. This information can inform treatment decisions and choice of colchicine or NSAID for prophylaxis when initiating allopurinol. Disclosure E. Roddy: None. R. Bajpai: None. H. Forrester: None. R. Partington: None. C.D. Mallen: Grants/research support; Keele University School Of Medicine has received funding from BMS to support a non-pharmacological atrial fibrillation screening study. L. Clarson: None. N. Padmanabhan: None. R. Whittle: None. S. Muller: None.

The Pattern of Allopurinol Prescription Among Chronic Kidney Disease Patients in a Tertiary Care Centre: A Single-Centre Experience.

ContextHyperuricemia is prevalent in patients with chronic kidney disease (CKD). Although it is associated with CKD incidence and progression, treating asymptomatic hyperuricemia with uric acid-lowering agents is still debatable.Aim of Workdetermine the rate of non-classical prescription of allopurinol in CKD patients.Settings and DesignThis was a retrospective study of adult patients prescribed allopurinol with CKD (stages 2–5) in Doctor Soliman Fakeeh Hospital (DSFH) Jeddah, Saudi Arabia, from 1/1/2016 to 1/1/2017.Subjects and MethodsEligible patients were identified from the hospital’s pharmacy system and cross-referenced with the electronic health records. Demographic data, laboratory results and indication as recorded by the prescribing physician were extracted. Prescriptions with no indication were categorized based on the uric acid levels. Hyperuricemia was documented as mild (6–10 mg/dL in females and 7–13 mg/dL in males) and severe (>13mg/dL in men and >10mg/dL in women).Statistical Analysis UsedDescriptive statistics (frequencies, percentages).ResultsFrom the 594 identified patients, 464 (78.1%) were males. A third of prescriptions (209/594) had no indication, 43.5% of which (91/209) had no documented uric acid levels, and 16.3% (34/209) had normal levels. Including patients with undocumented indication, 64.2% (381/594) were prescribed allopurinol for hyperuricemia, 86.4% of which (329/381) had mild hyperuricemia, and only 13.6% (52/381) had severe hyperuricemia. Other indications included malignancy-related disorders (6.2%, 37/594), gouty arthritis (5.2%, 31/594), and stones of unknown aetiology (3.4%, 20/594).ConclusionThe percentage of allopurinol prescription to patients with CKD without a clear indication in our centre was markedly high. This might increase the risk for side effects with no evidence-based benefits.

Hyperuricaemia, gout and allopurinol in the CKD Queensland registry

IntroductionThere is scant data on the role of hyperuricaemia, gout and allopurinol treatment in chronic kidney disease (CKD). Therefore, our aim is to investigate the possible associations between hyperuricaemia, gout, prescription of allopurinol and renal outcomes in patients with CKD.MethodsThe retrospective cohort study involved 1123 Royal Brisbane and Women’s Hospital (RBWH) patients, enrolled in the CKD.QLD registry from May 2011 to August 2017. Patients were divided into two uric acid categories, with uric acid ≤ 0.36 mmol/L and > 0.36 mmol/L. Association of delta estimated glomerular filtration rate (eGFR) with gout, allopurinol treatment and hyperuricaemia were analysed.ResultsPatients with an entry urate > 0.36 mmol/L were older, had higher body mass index (BMI) and worse baseline kidney function. Proportion of patients with gout, hyperuricaemia and allopurinol treatment increased with advanced CKD stages. Age-adjusted analysis revealed a significant association between serum urate level and delta eGFR, with no significant association between gout, treatment with allopurinol and delta eGFR. Furthermore, neither gout nor the prescription of allopurinol had a significant effect on the time to renal death (composite end point of kidney replacement therapy or death).ConclusionHyperuricaemia seemed to be independently associated with faster CKD progression or renal death. This was not observed with gout or prescription of allopurinol. Furthermore, allopurinol was not associated with decreased incidence of cardiovascular events. These data suggest that hyperuricaemia is likely the effect and not the cause of CKD or CKD progression.Graphic abstract

The pattern of allopurinol prescription in a university hospital practice

BackgroundAllopurinol as a drug is commonly used to treat gout and its complications. The aim usually is to lower the level of serum uric acid. Also, it was found to be prescribed in cases of asymptomatic hyperuricemia. However, this medication has serious side effects and some of these are fatal. So the aim of the current research work is to look at its use, whether properly indicated or not, in a university hospital.ResultsA total of 427 patients were included in this study. Only 3.7% (16) of the patients had the drug for significant hyperuricemia. Gout was confirmed in 40 (9.4%) patients.ConclusionIt is clear that most patients received allopurinol without proper indications. The inappropriate use of allopurinol should be looked at to reduce the cost of medication and more importantly to avoid possible adverse effects.

Clinical discussion: gout therapy in a comorbid patient

The data accumulated to date suggests that it is extremely rare for a gout patient to have only his or her main disease and no accompanying pathology. One of the frequent situations is a combination with another microcrystal arthritis, a disease of calcium pyrophosphate crystals deposition. In addition, diseases of the kidneys (including chronic renal failure), cardiovascular system, gastrointestinal tract, as well as metabolic disorders directly associated with gout or indirectly related to taking medications necessary to control the disease, not only affect the quality and longevity of life of the patient, but also create difficulties for its curation. The prescription of drug therapy, both symptomatic and pathogenetic, in such cases involves an assessment of all the associated risks, and the choice of drugs, in addition to efficiency, should be based on their safety profile in relation to comorbid pathology. This article analyzes the main principles and approaches to the treatment of gout and the disease of calcium pyrophosphate crystals deposition in the presence of concomitant diseases (arterial hypertension, chronic kidney disease, chronic heart failure, obesity, dyslipidemia, etc.) on the example of a 50-year-old patient. The possibilities of combined symptomatic therapy including colchicine, non-steroidal anti-inflammatory drugs and glucocorticoids are shown. The necessity and tactics of choice of preventive prophylactic therapy for arthritis attacks and use of phebuxostat in the presence of contraindications for prescription or ineffectiveness of allopurinol are also discussed.

Efficacy of febuxostat versus allopurinol and the predictors of achieving target serum urate in a cohort of Thai people with gout.

The objectives of our study were to compare the efficacy of febuxostat with allopurinol in Thai subjects with gout, as well as to determine the predictive factors of responsiveness to urate-lowering agents and to evaluate the safety of febuxostat in a real-world setting. The study was a retrospective cohort study; a total of 354 gout patients were recruited from February 2015 to November 2018. The patients were categorized according to prescription of allopurinol or febuxostat. Demographic data, comorbidities, concomitant medications, gout-related clinical parameters, and the laboratory results were collected. The serial serum urate (sUA) levels were recorded at the beginning of the treatment (baseline), and after treatment at 12weeks, 18weeks, and 27weeks. The primary efficacy endpoint was the achievement of target urate of < 6mg/dl in people taking febuxostat, compared with those taking allopurinol. The secondary endpoints were the predictive factors of achieving target urate level and adverse drug reactions in patients taking febuxostat. Multivariable regression analysis was used to determine factors associated with achieving target serum urate. After the treatment, the febuxostat groups had significantly lower mean sUA compared with the allopurinol groups across all follow-up periods. The proportion of people who achieved target serum urate was also higher in the febuxostat groups compared with the allopurinol groups throughout the follow-up periods. The multivariable regression analysis showed that febuxostat 40mg (OR = 10.96 (95% CI 4.32-27.80); p value < 0.001), febuxostat 80mg (OR = 9.54 (95% CI 3.91-23.28), smoking (OR = 2.35 (95% CI 1.13-4.91); p value = 0.023), and low baseline serum urate (OR = 0.62 (95% CI 0.52-0.74); p value <0.001) were associated with the achievement of target serum urate. No adverse drug reaction from febuxostat was observed even among people with renal insufficiency. In a Thai cohort, people receiving febuxostat are more likely to achieve target serum urate level, compared with people receiving allopurinol. Febuxostat (40 or 80mg), smoking, and low baseline serum urate were associated with the achievement of target serum urate. • Febuxostat showed superior urate-lowering efficacy compared with allopurinol in an Asian population. • In addition to febuxostat, lower baseline serum urate level and history of smoking were associated with achieving target serum urate in gout patients.

Allopurinol prescription patterns among patients in a Saudi tertiary care centre.

ObjectivePhysicians frequently prescribe allopurinol for uric acid deposition disorders. However, reports have emerged of the inappropriate use and overprescription of allopurinol. We conducted this study to determine the rate of inappropriate prescription of allopurinol in a Saudi institution.MethodsThis cross-sectional descriptive study was conducted on all adult patients who had been prescribed allopurinol in Doctor Soliman Fakeeh Hospital Jeddah KSA. Demographic data and laboratory results were retrieved from patients’ electronic health records (EHR). We considered valid indications of allopurinol as significant hyperuricemia (>13 mg/dL in men and >10 mg/dL in women), confirmed gout, hyperuricosuria of more than 1100 mg/day, uric acid stones or recurrent calcium oxalate kidney stones, malignancy, and haemolysis. The possible valid indications were unconfirmed gout and unconfirmed type of kidney stones, whereas no documented indication or insignificant hyperuricemia was considered as an invalid indication.ResultsWe included 1978 patients in this study. The cohort was composed of 76.4% men and 23.6% women. The mean ± standard deviation of age of this patient cohort was 53 and 4 months ± 15 years. The mean ± standard deviation of duration since the first prescription was 1.53 ± 2.2 years. Physicians prescribed allopurinol without a valid indication in 1539 patients (77.8%). More than a third of the patients (39%) did not have a documented indication and 38.8% were prescribed allopurinol for insignificant hyperuricemia.ConclusionThis study revealed a markedly high number of allopurinol prescriptions without a clear indication in our centre. This approach may potentially expose patients to serious side effects of allopurinol without added benefits.

Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data

ObjectiveTo assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study.MethodsWe used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify...

Development of a HLA-B*58:01 Allele Screening System for Allopurinol-Induced Severe Cutaneous Adverse Reactions Detection

The HLA-B*58:01 allele has been identified as a genetic marker in the fatal allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, the screening of the HLA-B*58:01 allele prior to allopurinol prescription has not been implemented in hospitals, mostly due to the absence of an inexpensive and rapid screening method. In this work, we have developed a HLA-B*58:01 allele screening system which is able to give results in one and a half hour and is cheaper than any other screening instruments available. The system uses the High-Resolution Melt (HRM) method and generates difference melt curves proportional to a specific DNA’s sequence. A positive screening result will be shown if the HLA-B*58:01 allele is detected in unknown samples screened. Twelve HRM experiments were performed to optimize the system and six final optimized experiments are shown in this article, along with their difference melt curves. The system was successfully benchmarked against the Illumina Eco Real Time machine and results were also validated by Sanger sequencing. The system was also compared against other HLA screening methods available on the market. We propose that the implementation of this HLA-B*58:01 screening system in hospitals will help to decrease the number of SCARs cases and eventually eliminate them in the long run. Patients will thus be prescribed allopurinol only if they test negative for the HLA-B*58:01 gene and those who test positive will be given alternative drugs, ultimately saving lives, time of treatment and overall medical cost.

Twenty-Four Hour Urine Testing and Prescriptions for Urinary Stone Disease-Related Medications in Veterans.

Current guidelines recommend 24-hour urine testing in the evaluation and treatment of persons with high-risk urinary stone disease. However, how much clinicians use information from 24-hour urine testing to guide secondary prevention strategies is unknown. We sought to determine the degree to which clinicians initiate or continue stone disease-related medications in response to 24-hour urine testing. We examined a national cohort of 130,489 patients with incident urinary stone disease in the Veterans Health Administration between 2007 and 2013 to determine whether prescription patterns for thiazide diuretics, alkali therapy, and allopurinol changed in response to 24-hour urine testing. Stone formers who completed 24-hour urine testing (n=17,303; 13%) were significantly more likely to be prescribed thiazide diuretics, alkali therapy, and allopurinol compared with those who did not complete a 24-hour urine test (n=113,186; 87%). Prescription of thiazide diuretics increased in patients with hypercalciuria (9% absolute increase if urine calcium 201-400 mg/d; 21% absolute increase if urine calcium >400 mg/d, P<0.001). Prescription of alkali therapy increased in patients with hypocitraturia (24% absolute increase if urine citrate 201-400 mg/d; 34% absolute increase if urine citrate ≤200 mg/d, P<0.001). Prescription of allopurinol increased in patients with hyperuricosuria (18% absolute increase if urine uric acid >800 mg/d, P<0.001). Patients who had visited both a urologist and a nephrologist within 6 months of 24-hour urine testing were more likely to have been prescribed stone-related medications than patients who visited one, the other, or neither. Clinicians adjust their treatment regimens in response to 24-hour urine testing by increasing the prescription of medications thought to reduce risk for urinary stone disease. Most patients who might benefit from targeted medications remain untreated.

Association between allopurinol use and hepatocellular carcinoma in a case–control study in Taiwan

Background/objectivesLittle is known about the role of allopurinol use on the risk of hepatocellular carcinoma (HCC). The study aimed to examine the association between allopurinol use and HCC in Taiwan.MethodsUsing...